Polyarteritis Nodosa - PAN

  • Diagnosis
  • Algorithms
  • Background
  • Pediatrics
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Unexplained systemic illness with multiple system involvement (renal, neurologic, dermatologic)

Laboratory Testing

  • Nonspecific testing – helpful in excluding other diagnoses or identifying organ dysfunction
    • CBC – rule out infection
    • Urinalysis (UA) – hematuria, proteinuria, red blood cell casts
    • C-reactive protein (CRP)
  • Testing to consider to rule out other diagnoses
    • ANCA – rarely positive, to rule out ANCA-associated vasculitis
    • Hepatitis B surface antigen – rule out concomitant chronic hepatitis
    • ANA – rule out connective tissue diseases
    • Antiglomerular basement membrane antibodies – rule out an antiglomerular basement membrane disease (anti-GBM)

Histology

  • Small- and medium-size artery necrotizing vasculitis with absence of glomerulonephritis
  • Arterioles, capillaries and/or venules – most affected
  • Immunofluorescence fails to demonstrate complement or immunoglobulin in vessel walls

Imaging studies

  • Angiography – microaneurysms and stenoses of medium vessels

Differential Diagnosis

Polyarteritis nodosa (PAN) is a necrotizing vasculitis resulting in aneurysmal formation and organ infarction. It is categorized as a medium vessel vasculitis (Chapel Hill, 2012).

Epidemiology

  • Incidence –16-25/1,000,000 for systemic vasculitis as a group (includes eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis, polyarteritis nodosa and granulomatosis with polyangiitis)
  • Age – peak onset in 50s
  • Sex – M:F, equal

Risk Factors

Clinical Presentation

  • Constitutional – fever, malaise, weight loss, arthralgias
  • Cardiovascular – coronary artery disease
  • Dermatological – vascular purpura, livedo reticularis, lower extremity ulcers, subcutaneous ulcers
  • Gastrointestinal – nonspecific abdominal pain, gastrointestinal bleeding, bowel perforation
  • Neurological – mononeuropathy multiplex
  • Renal – renovascular hypertension, vascular nephropathy

Clinical Background

Epidemiology

  • Age – peak is 9-11 years
  • Sex – M<F, slight

Clinical Presentation

  • Tends to be a more limited disorder than in adults
  • Constitutional – fever, malaise, weight loss
  • Musculoskeletal – arthritis/arthralgia, myositis, myalgia
  • Renal – vascular hypertension, hematuria, proteinuria
  • Neurological – peripheral neuropathy
  • Gastrointestinal – nonspecific abdominal pain
  • Dermatological – livedo reticularis, skin nodules, skin infections

Diagnosis

Indications for testing

  • Unexplained systemic illness with multiple system involvement (renal, neurologic, dermatologic)

Laboratory testing

  • Nonspecific testing
    • CBC – anemia, leukocytosis, thrombocytoses
    • C-reactive protein (CRP)
    • Urinalysis (UA) – proteinuria, hematuria, red cell casts
    • Electrolytes – increases in BUN/Cr not uncommon
  • ANCA – rarely positive

Histology

  • Small- and medium-size artery necrotizing vasculitis in the absence of glomerulonephritis
  • Vasculitis in arterioles, capillaries or venules
  • Immunofluorescence fails to demonstrate complement or immunoglobulin in vessel walls

Imaging studies

  • Angiography – microaneurysms and stenoses of medium vessels

Differential Diagnosis

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Recommended Use 

Identify anemia, leukocytosis, thrombocytoses

C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Recommended Use 

Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, rheumatoid arthritis, infection, or sepsis)

Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Recommended Use 

Screen for various metabolic and kidney disorders

Limitations 

Not specific for diagnosis of PAN

Anti-Nuclear Antibodies (ANA), IgG by ELISA with Reflex to ANA, IgG by IFA 0050080
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Recommended Use 

Aid in initial diagnosis of connective tissue disease

All ELISA results reported as Detected are further tested by IFA

ANA ELISA screen is designed to detect antibodies against dsDNA, histone, SS-A (Ro), SS-B (La), Smith, snRNP/Sm, Scl-70, Jo-1, centromere, and an extract of lysed HEp-2 cells

Reflex pattern – if ANA are detected by ELISA, then ANA by IFA titer will be added

Limitations 

Results are not disease specific

ANA ELISA assays have been reported to have lower sensitivities for antibodies associated with nucleolar and specked ANA-IFA patterns

Anti-Neutrophil Cytoplasmic Antibody with Reflex to Titer and MPO/PR-3 Antibodies 2002068
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay

Recommended Use 

Preferred reflex panel for managing patients with a known diagnosis of vasculitis; may be assistive in evaluating suspected vasculitis

For the workup of suspected vasculitis, the preferred panel is ANCA-associated vasculitis profile (ANCA/MPO/PR-3) with reflex to ANCA titer

Panel includes ANCA, IgG; myeloperoxidase antibody and serine protease 3 antibody

Reflex pattern – if screen is positive, titer and MPO/PR-3 antibodies testing will be added to aid in antibody determination

Limitations 

Not specific for diagnosis of PAN

Hepatitis B Virus Surface Antigen with Reflex to Confirmation 0020089
Method: Qualitative Chemiluminescent Immunoassay 

Recommended Use 

Can be ordered as part of the acute hepatitis panel which includes HAV IgM, HBV core antibody IgM, HBV surface antigen, and HCV antibody; refer to acute hepatitis panel with reflex to HBsAg confirmation

Reflex pattern – if results for HBsAg screen are repeatedly reactive with an index value between 1.00 and 50.00, then HBsAg confirmation will be added

Glomerular Basement Membrane Antibody, IgG by Multiplex Bead Assay and IFA 2008403
Method: Semi-Quantitative Multiplex Bead Assay/Qualitative Indirect Fluorescent Antibody

Recommended Use 

Detect glomerular basement membrane (GBM) antibodies in suspected or established anti-GBM disease
Panel includes GBM antibody, IgG by multiplex bead assay and IFA

Limitations 

False positive results may occur due to reactivity against other chains of type IV collagen

Follow-up 

Positive result should be confirmed by renal biopsy

Guidelines

Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Sep 2017]

Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013; 65(1): 1-11. PubMed

Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, Buoncompagni A, Lazar C, Bilge I, Uziel Y, Rigante D, Cantarini L, Hilario MO, Silva CA, Alegria M, Norambuena X, Belot A, Berkun Y, Estrella AI, Olivieri AN, Alpigiani MG, Rumba I, Sztajnbok F, Tambic-Bukovac L, Breda L, Al-Mayouf S, Mihaylova D, Chasnyk V, Sengler C, Klein-Gitelman M, Djeddi D, Nuno L, Pruunsild C, Brunner J, Kondi A, Pagava K, Pederzoli S, Martini A, Ruperto N, Paediatric Rheumatology International Trials Organisation (PRINTO). EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis. 2010; 69(5): 798-806. PubMed

Ruperto N, Ozen S, Pistorio A, Dolezalova P, Brogan P, Cabral DA, Cuttica R, Khubchandani R, Lovell DJ, O'Neil KM, Quartier P, Ravelli A, Iusan SM, Filocamo G, Magalhães CS, Unsal E, Oliveira S, Bracaglia C, Bagga A, Stanevicha V, Manzoni SM, Pratsidou P, Lepore L, Espada G, Kone-Paut I, Paut IK, Zulian F, Barone P, Bircan Z, Maldonado Md, Russo R, Vilca I, Tullus K, Cimaz R, Horneff G, Anton J, Garay S, Nielsen S, Barbano G, Martini A, Paediatric Rheumatology International Trials Organisation (PRINTO). EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part I: Overall methodology and clinical characterisation. Ann Rheum Dis. 2010; 69(5): 790-7. PubMed

General References

Harrold LR, Liu NY. Polyarteritis nodosa presenting as pancytopenia: case report and review of the literature. Rheumatol Int. 2008; 28(10): 1049-51. PubMed

Kallenberg CG. The last classification of vasculitis. Clin Rev Allergy Immunol. 2008; 35(1-2): 5-10. PubMed

Pettigrew D, Teuber SS, Gershwin E. Polyarteritis nodosa. Compr Ther. 2007; 33(3): 144-9. PubMed

Medical Reviewers

Slev, Patricia R., PhD, Medical Director, Serological Hepatitis/Retrovirus, Immunology Core; Co-Medical Director, Microbial Immunology and Immunogenetics; Chief Medical Director, Immunology Division at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Tebo, Anne E., PhD, D(ABMLI), Medical Director, Immunology at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Antiglomerular Basement Membrane Disease - Goodpasture Syndrome
Connective Tissue Diseases
Eosinophilic Granulomatosis with Polyangiitis - EGPA
Giant Cell Arteritis - Temporal Arteritis
Granulomatosis with Polyangiitis - GPA
Hepatitis B Virus - HBV
IgA Vasculitis - Henoch Schönlein Purpura
Microscopic Polyangiitis - MPA
Vasculitis

Last Update: July 2017